New perspectives on epigenetic modifications and PARP inhibitor resistance in HR-deficient cancers  

作　　者：Rachel Bayley Ellie Sweatman Martin R.Higgs 

机构地区：[1]Institute of Cancer and Genomic Sciences,University of Birmingham,Birmingham B152TT,UK

出　　处：《Cancer Drug Resistance》2023年第1期35-44,共10页癌症耐药（英文）

基　　金：supported by a PhD studentship from the University of Birmingham and Cancer Research UK(C17422/A25154)awarded to Sweatman E and Higgs MR;a Breast Cancer Now project grant(2019AugPR1320)supporting Bayley R(awarded to Garcia P);an MRC Career Development Fellowship(MR/P009085/1)awarded to Higgs MR.

摘　　要：The clinical treatment of DNA-repair defective tumours has been revolutionised by the use of poly(ADP)ribose polymerase(PARP)inhibitors.However,the efficacy of these compounds is hampered by resistance,which is attributed to numerous mechanisms including rewiring of the DNA damage response to favour pathways that repair PARP inhibitor-mediated damage.Here,we comment on recent findings by our group identifying the lysine methyltransferase SETD1A as a novel factor that conveys PARPi resistance.We discuss the implications,with a particular focus on epigenetic modifications and H3K4 methylation.We also deliberate on the mechanisms responsible,the consequences for the refinement of PARP inhibitor use in the clinic,and future possibilities to circumvent drug resistance in DNA-repair deficient cancers.

关 键 词：Double strand break repair histone methylation PARP inhibitor RESISTANCE SETD1A BOD1L H3K4 

分 类 号：R730[医药卫生—肿瘤]